Protection of the endothelial glycocalyx by antithrombin in an endotoxin-induced rat model of sepsis

Thromb Res. 2018 Nov:171:1-6. doi: 10.1016/j.thromres.2018.09.042. Epub 2018 Sep 6.

Abstract

Introduction: Injury and loss of the endothelial glycocalyx occur during the early phase of sepsis. We previously showed that antithrombin has a protective effect on this structure in vitro. Here, we investigated the possible protective effects of antithrombin in an animal model of sepsis.

Methods: Wistar rats were injected with endotoxin, and circulating levels of syndecan-1, hyaluronan, albumin, lactate and other biomarkers were measured in an antithrombin-treated group and an untreated control group (n = 6 in each group). Intravital microscopy was used to observe leukocyte adhesion, microcirculation, and syndecan-1 staining.

Results: The circulating levels of syndecan-1 and hyaluronan were significantly reduced in the antithrombin-treated group, compared with the untreated controls. Lactate levels and albumin reduction were significantly attenuated in the antithrombin-treated group. Intravital microscopic observation revealed that both leukocyte adhesion and blood flow were better maintained in the treatment group. The syndecan-1 lining was disrupted after endotoxin treatment, and this derangement was attenuated by treatment with antithrombin.

Conclusion: Antithrombin effectively maintained microcirculation and vascular integrity by protecting the glycocalyx in a rat sepsis model.

Keywords: Antithrombin; Endothelium; Hyaluronan; Inflammation; Microcirculation; Sepsis; Syndecan-1.

MeSH terms

  • Animals
  • Antithrombin Proteins / therapeutic use*
  • Antithrombins / therapeutic use*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / pathology
  • Endotoxins / immunology
  • Glycocalyx / drug effects*
  • Glycocalyx / immunology
  • Glycocalyx / pathology
  • Hyaluronic Acid / blood
  • Hyaluronic Acid / immunology
  • Inflammation / blood
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / pathology
  • Microcirculation / drug effects
  • Rats, Wistar
  • Sepsis / blood
  • Sepsis / drug therapy*
  • Sepsis / immunology
  • Sepsis / pathology*
  • Syndecan-1 / blood
  • Syndecan-1 / immunology

Substances

  • Antithrombin Proteins
  • Antithrombins
  • Endotoxins
  • Syndecan-1
  • Hyaluronic Acid